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Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability (SIPEXI)

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ClinicalTrials.gov Identifier: NCT02270736
Recruitment Status : Completed
First Posted : October 21, 2014
Results First Posted : January 20, 2021
Last Update Posted : August 10, 2021
Sponsor:
Information provided by (Responsible Party):
Merz Pharmaceuticals GmbH

Brief Summary:
The objective of this study is to investigate the efficacy and safety of NT 201 compared with placebo for the treatment of chronic troublesome sialorrhea associated with neurological disorders (e.g. cerebral palsy, traumatic brain injury) and/or intellectual disability in children and adolescents naïve to Botulinum neurotoxin treatment and aged 2-17 years.

Condition or disease Intervention/treatment Phase
Chronic Troublesome Sialorrhea Cerebral Palsy Stroke Traumatic Brain Injury Intellectual Disability Drug: NT 201 Placebo Drug: NT 201 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 256 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study With an Open-label Extension Period to Investigate the Efficacy and Safety of NT 201 in the Treatment of Children and Adolescents (2-17 Years) With Chronic Troublesome Sialorrhea Associated With Neurological Disorders, and/or Intellectual Disability
Actual Study Start Date : February 9, 2015
Actual Primary Completion Date : February 23, 2018
Actual Study Completion Date : May 7, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Double-blind MP: Placebo (Age 6 to 17 Years)
Participants will receive placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes will be matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Drug: NT 201 Placebo
NT 201 placebo matching injection.

Experimental: Double-blind, MP: NT 201 (Age 6 to 17 Years)
Participants will receive NT 201 (up to 2.5 Units per kilogram [U/kg] body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Drug: NT 201
NT 201 injection.
Other Names:
  • IncobotulinumtoxinA
  • Xeomin
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins

Experimental: Open-label, MP: NT 201 (Age 2 to 5 Years)
Participants will receive NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Drug: NT 201
NT 201 injection.
Other Names:
  • IncobotulinumtoxinA
  • Xeomin
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins

Experimental: OLEX: NT 201 (Age 6 to 17 Years)
Participants will receive NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm will consist of participants who will participate in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)".
Drug: NT 201
NT 201 injection.
Other Names:
  • IncobotulinumtoxinA
  • Xeomin
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins

Experimental: OLEX: NT 201 (Age 2 to 5 Years)
Participants will receive NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).
Drug: NT 201
NT 201 injection.
Other Names:
  • IncobotulinumtoxinA
  • Xeomin
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins




Primary Outcome Measures :
  1. Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4 [ Time Frame: Baseline and Week 4 ]
    This endpoint was planned to be analyzed in double-blind, MP, 6 to 17 years participants only. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and the procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea.

  2. Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s) [ Time Frame: Week 4 ]
    This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).

  3. Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle [ Time Frame: Baseline up to Week 64 ]

Secondary Outcome Measures :
  1. Change From Baseline in uSFR at Weeks 8 and 12 [ Time Frame: Baseline and Weeks 8 and 12 ]
    This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and then procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea.

  2. GICS at Weeks 8 and 12 [ Time Frame: Weeks 8 and 12 ]
    This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).

  3. Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle [ Time Frame: Baseline up to Week 64 ]
  4. Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle [ Time Frame: Baseline up to Week 64 ]
  5. Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle [ Time Frame: Baseline up to Week 64 ]
  6. Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle [ Time Frame: Baseline up to Week 64 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female child/adolescent age 2-17 years.
  • Any neurological disorder (e.g. cerebral palsy or traumatic brain injury) and/or intellectual disability associated with chronic troublesome sialorrhea for at least 3 months up to the screening. In subjects with intellectual disability (ID) without neurological disorders, a diagnosis of ID by a specialist, e.g. pediatrician or by a center for developmental medicine is required for inclusion.
  • Severe drooling (modified Teacher´s Drooling Scale [mTDS] ≥ 6; clothing occasionally becomes damp) as rated by the investigator.
  • Parental consent and the subject's oral or written assent as the subject is able to provide.

Exclusion Criteria:

  • Chronic troublesome sialorrhea not related to neurological disorders and/or intellectual disability.
  • Body weight < 12 kg.
  • Pharmacological treatment for sialorrhea or concomitant medication known to influence sialorrhea strongly (e.g. anticholinergics with exception of locally applied or short acting drugs used under general anesthesia) within 45 days before baseline and during the entire study period.
  • Any previous known or suspected hypersensitivity to Botulinum toxin.
  • Aspiration pneumonia within 6 month before screening.
  • Any previous treatment with Botulinum toxin for any body region during the year before screening or within the screening period
  • Prior, concomitant or planned surgery or irradiation to head and neck to control sialorrhea (including salivary gland surgery or salivary gland irradiation) within one year before screening or planned for any part of the entire study period.
  • Concurrent diseases, including hematological, hepatic, renal, gastrointestinal, endocrine, pulmonary, musculoskeletal, or psychiatric diseases or conditions, which in the judgment of the investigator would put the subject at risk while in the study, could influence the results of the study, or negatively impact the subject's ability to participate in the study.
  • Extremely poor dental and/or oral condition that might preclude safe study participation by the judgment of the investigator.
  • Nursing mother or pregnant female subject.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02270736


Locations
Show Show 31 study locations
Sponsors and Collaborators
Merz Pharmaceuticals GmbH
Investigators
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Study Director: Merz Medical Expert Merz Pharmaceuticals GmbH
  Study Documents (Full-Text)

Documents provided by Merz Pharmaceuticals GmbH:
Study Protocol  [PDF] June 16, 2016
Statistical Analysis Plan  [PDF] June 21, 2019

Publications of Results:
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Responsible Party: Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT02270736    
Other Study ID Numbers: MRZ60201_3091_1
2013-004532-30 ( EudraCT Number )
First Posted: October 21, 2014    Key Record Dates
Results First Posted: January 20, 2021
Last Update Posted: August 10, 2021
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sialorrhea
Brain Injuries
Brain Injuries, Traumatic
Cerebral Palsy
Intellectual Disability
Nervous System Diseases
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Brain Damage, Chronic
Neurobehavioral Manifestations
Neurologic Manifestations
Neurodevelopmental Disorders
Mental Disorders
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Botulinum Toxins
Botulinum Toxins, Type A
abobotulinumtoxinA
incobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents